Genetic heterogeneity in familial juvenile polyposis

Juvenile polyposis syndrome (JPS) Is an autosomal dominant syndrome charact erized by multiple gastrointestinal hamartomatous polyps in the absence of the extraintestinal features that are classic for other hamartomatous polyp osis syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden disease (CD), About 50% of ERRS and > 80% of CD demonstrate germ-line muta tions in the tumor suppressor and dual phosphatase, PTEN, Germ-line mutatio n of PTEN as a cause for JPS in a child is controversial because extraintes tinal manifestations that would exclude JPS could appear after adolescence, altering the clinical diagnosis, Here, we investigated a family in which t he 55-year-old father, who lacks thyroid or skin findings characteristic of CD, demonstrated a germ-line mutation in PTEN that was passed to identical twin daughters, who both manifested JPS, The mutation was a deletion of fi ve bases beginning seven bases from the start of exon 4 of PTEN, which caus ed aberrant transcripts by reverse transcription-PCR that were absent from a normal individual. Thus, mutations in PTEN are associated with JPS in add ition to CD and some ERRS families, although the incidence of PTEN germ-lin e mutations in JPS might be more rare than that reported for SMAD4, a gene found to be mutated in approximately one-half of the JPS families investiga ted.